This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This application addresses broad Challenge Area (15): 15-NS-102: Translation of Gene Silencing Therapeutics. The proposed challenge set forth in the RFA is to extend the current understanding of the feasibility and safety of RNA interference (RNAi) therapeutics for the treatment of chronic neurological disorders from rodent models of disease to a more clinically relevant species. The current proposal outlines a systematic approach to translate work we, and others, have undertaken to investigate RNAi as a potential therapy for the neurological disorder, Huntington's disease (HD) in cell culture and rodent models and apply these findings to the non-human primate (NHP). The proposed studies are a collaboration between two laboratories: the Davidson Laboratory at the University of Iowa and the Ojeda Laboratory at the Oregon National Primate Research Center (ONPRC). The Davidson Laboratory has experience developing and testing RNAi therapeutics in rodents, while the Ojeda Laboratory has expertise in stereotaxic delivery of viral vectors to the NHP brain. Also, the ONPRC has methodologies, equipment and personnel in place that, along with Dr. Ojeda's group, can evaluate if application of HTT suppression, or RNAi in general, induces neuropathology or neurological symptoms after delivery of RNAi expression vectors to NHP brain.